Lymphedema, a swelling of the upper extremity due to an accumulation of protein rich interstitial fluid, significantly impacts the quality of life of patients who develop this complication following their treatment for breast cancer. Lymphedema incidence is reported to be widely variable with most experts conceding an incidence rate of approximately 25 percent, with onset occurring at any time post treatment. As survival from breast cancer continues to improve, addressing complications of treatment and its ensuing impact on quality of life necessitate strong evidence based interventions. Currently, the treatment of lymphedema has been largely based on clinician experience and a growing body of clinical trial data that suffers from lack of adequately sized samples and methodological challenges, particularly short-term follow-up. Interventions often require access to specially trained therapists and demand considerable time and dexterity from patients and their caregivers resulting in further illness burden and diminished quality of life. The proposed trial will attempt to address lymphedema with a novel approach based on early identification of mild, pre-clinical lymphedema. The sample will include screening of all new patients diagnosed with breast cancer in a large urban comprehensive cancer center averaging 1000 new breast cancer diagnoses per year. All new patients will be asked to participate in lymphedema screening using Perometer measurements and completion of the Massachusetts General Hospital Upper Extremity Impairments Following Treatment for Breast Cancer Survey. The Perometer is considered the gold standard in arm volume measurement, and is accurate within 1 percent. Arm volume measurements will be obtained at baseline (prior to any surgical intervention), before and after each treatment and at least twice per year for 5 years. All patients will receive standard of care treatment following definitive breast surgery including the Lymphedema Patient Education Sheet and exercises for regaining shoulder motion post operatively. We hypothesize that if lymphedema is detected early enough (at the onset of 5-10 percent volume difference between the patients two arms), early treatment will prevent progression and improve quality of life. Subjects who develop mild lymphedema of 5-10 percent will be randomized between observation and compression therapy for 8 weeks (n=208 pts). Subjects with moderate lymphedema of 11-20 percent volume difference will be randomized to compression sleeve therapy with and without night time compression wrapping (n=128 pts). Information from this trial should yield data that will bring clarity to the natural history of lymphedema, efficacy of early intervention, and the impact of lymphedema on functional impairment and quality of life. PUBLIC HEALTH RELEVANCE: Project Narrative Lymphedema is a distressing swelling of the arm and chest that can occur after breast cancer treatment. Our study aims to evaluate whether early identification and treatment can decrease the rate of lymphedema and improve the quality of life of women who suffer from this devastating complication of treatment.